LbL-coated medical device and method for making the same

ABSTRACT

The present invention provides a medical device, preferably an ophthalmic device, more preferably a contact lens, which comprises a core material and a biocompatible LbL coating non-covalently attached to said core material. The biocompatible LbL coating comprises at least one charge/non-charge bilayer, wherein said charge/non-charge bilayer is composed of, in no particular order, one layer of a charged polymeric material and one layer of a non-charged polymeric material which is capable of being non-covalently bond to the charged polymeric material.

This application claims the benefit under USC §119)e) of U.S.provisional application No. 60/409,950 filed Sep. 11, 2002, incorporatedby reference in its entirety.

The present invention generally relates to a medical device having abiocompatible LbL coating thereon. In particular, the present inventionrelates to an ophthalmic device having a biocompatible LbL coating thatcomprises at least one bilayer of a charged polymeric material and anon-charged polymeric material which is non-covalently bonded to thecharged polymeric material. In addition, this invention provides amethod for making a medical device having a biocompatible LbL coating ofthe invention.

BACKGROUND OF THE INVENTION

Many devices used in biomedical applications require that the bulk ofthe devices have one property and the surfaces of the device have adifferent property. For example, contact lenses may require relativelyhigh oxygen permeability through the bulk of the lens to maintain goodcorneal health. However, materials that exhibit exceptionally highoxygen permeability (e.g. polysiloxanes) are typically hydrophobic and,will up take lipid or protein from the ocular environment and may adhereto the eye if not treated or surface-modified. Thus, a contact lens willgenerally have a core or bulk material that is highly oxygen permeableand hydrophobic, and a surface that has been treated or coated toincrease hydrophilic properties. This hydrophilic surface allows thelens to move relatively freely on the eye without absorbing excessiveamounts of tear lipid and protein.

In order to modify the hydrophilic nature of a relatively hydrophobiccontact lens material, a coating may be applied onto the surface of acontact lens using a number of technologies, including a plasmatreatment process (e.g., PCT Publication Nos. WO 96/31793, WO 99/57581,WO 94/06485), a Langmuir-Blodgett deposition process (e.g., U.S. Pat.Nos. 4,941,997; 4,973,429; and 5,068,318), a controlled spin castingprocess, a chemisorption process, a vapor deposition or a layer-by-layerpolymer adsorption process that is preceded by a charge inducingprocess. These techniques are not cost-effective and are difficult to beimplemented in an automated production process.

Another coating technique is a layer-by-layer (“LbL”) polyelectrolyteabsorption process. For example, Yoo, et al. reported a process whichinvolves alternatively dipping hydrophilic glass substrates in apolyelectrolyte solution (e.g., polycations such as polyallylamine orpolyethyleneimine) and then in an oppositely charged solution to formelectrically conducting thin films and light-emitting diodides (LEDs)(Yoo, et al., “Investigation of New Self-Assembled Multilayer Thin FilmsBased on Alternately Adsorbed Layers of Polyelectrolytes and FunctionalDye Molecules”, Mat. Res. Soc. Symp. Proc. 413: 395400 (1996)).

A series of three articles described similar LbL polyelectrolyteabsorption processes (Ferreira & Rubner, Macromolecules, 28: 7107-7114(1995); Fou & Rubner, Macromolecules, 28: 7115-7120 (1995); and Cheunget al., Macromolecules, 30:2712-2716 (1997)). These processes involvetreating glass substrates that have hydrophilic, hydrophobic,negatively, or positively charged surfaces. The glass surfaces aretreated for extended periods in hot acid baths and peroxide/ammoniabaths to produce a hydrophilic surface. Hydrophobic surfaces areproduced by gas-phase treatment in the presence of1,1,1,3,3,3-hexamethyldisilazine for 36 hours. Charged surfaces areprepared by covalently anchoring charges onto the surface of thehydrophilic slides. For example, positively charged surfaces are made byfurther treating the hydrophilic surfaces in methanol, methanol/toluene,and pure toluene rinses, followed by immersion in (N-2aminoethyl-3-aminopropyl) trimethyloxysilane solution for 12 to 15hours. This procedure produces glass slides with amine functionalities,which are positively charged at a low pH.

U.S. Pat. Nos. 5,518,767 and 5,536,573 to Rubner et al. describe methodsof producing bilayers of p-type doped electrically conductivepolycationic polymers and polyanions or water-soluble, non-ionicpolymers on glass substrates. These patents describe extensive chemicalpre-treatments of glass substrates that are similar to those describedin the aforementioned articles.

U.S. Pat. No. 5,208,111 to Decher et al. describes a method for applyingone or more layers to a support modified by the applications of ions andionizable compounds of the same charges over the entire area. The one ormore layers are made of organic materials which in each layer containions of the same charge, the ions of the first layer having the oppositecharge of the modified support and in the case of several layers eachfurther layer having again the opposite charge of the previous layer.

U.S. Pat. No. 5,700,559 to Sheu et al. discloses a method for making ahydrophilic article having a substrate, an ionic polymeric layer bondeddirectly onto the substrate, and a disordered polyelectrolyte coatingionically bonded to the ionic polymeric layer. The ionic polymeric layeris obtained by a plasma treatment, an electron beam treatment, a coronadischarge, an X-ray treatment, or an acid/base chemical modification ofthe substrate.

Although each of these surface modification techniques are effective forproducing an article with a surface that is different from the remainderof the article, the modification processes requires complex andtime-consuming pretreatment of the substrate surface. To overcome thisproblem, various layer-by-layer (LbL) polyelectrolyte depositiontechniques have been developed by the assignee of the present invention(e.g., PCT Publication Nos. WO 01/57118, WO 99/35520). Theselayer-by-layer techniques effectively alter the surfaces of variousmaterials, such as contact lenses. One layer-by-layer (LbL) coatingtechnique involves consecutively dipping a substrate into oppositelycharged polymeric materials until a coating of a desired thickness isformed. In addition, another technique that results in a layer-by-layercoating while avoiding the time-consuming aspects of sequential dipping,is the single dip process disclosed in co-pending U.S. PatentApplication Ser. No. 60/180,463 filed on Feb. 4, 2000, entitled“Single-Dip Process for Achieving a Layer-by-Layer-Like Coating”, whichapplies charged polymeric material onto the substrate with only a singledip. In this technique, a generally hydrophobic article such as acontact lens is dipped into a single charged polymeric solutioncontaining at least one polycationic material and at least onepolyanionic material. The polycationic material may include a positivelycharged moiety such as poly(allyl amine hydrochloride) and thepolyanionic material may include a negatively charged moiety such aspolyacrylic acid. Typically, the charged polymeric components areemployed in non-stoichometric amounts such that one of the components ispresent within the solution in a greater amount than another component.

Each of these LbL-coating techniques is effective for producing anarticle with a surface that is different from the remainder of thearticle. However, these LbL-coating techniques require at least twooppositely charged polymeric materials and an article having an LbLcoating produced therefrom may have a highly charged surface. A contactlens having a highly charged surface may be susceptible to thedepositions of some proteins on the lens surface and/or may causeundesirable adverse effects on the wearer's comfort and/or ocularhealth. Therefore, it would be desirable if an LbL-coating process canbe developed to produce coated articles having a significantly decreasedcharge density.

SUMMARY OF THE INVENTION

One object of the invention is to provide a method for making apolymeric article with a biocompatible LbL coating which comprises atleast one charge/non-charge bilayer, wherein said charge/non-chargebilayer is composed of, in no particular order, one layer of a chargedpolymeric material and one layer of a non-charged polymeric materialwhich is capable of being non-covalently bonded to the charged polymericmaterial.

Another object of the invention is to provide a polymeric articles witha biocompatible LbL coating which has a relatively low charge densityand a relatively high hydrophilicity and lubricity.

These and other objects of the invention are met by the various aspectsof the invention described herein.

The invention, in one aspect, provides a polymeric article, preferablyan ophthalmic device, more preferably a contact lens, having abiocompatible LbL coating which comprises at least one charge/non-chargebilayer, wherein said charge/non-charge bilayer is composed of, in noparticular order, one layer of a charged polymeric material and onelayer of a non-charged polymeric material which is capable of beingnon-covalently bonded to the charged polymeric material.

The invention, in another aspect, provides a method of making apolymeric article, preferably, an ophthalmic device, more preferably acontact lens, having a biocompatible LbL coating, wherein thebiocompatible LbL coating comprises at least one charge/non-chargebilayer, wherein said charge/non-charge bilayer is composed of, in noparticular order, one layer of a charged polymeric material and onelayer of a non-charged polymeric material which is capable of beingnon-covalently bonded to the charged polymeric material. The method ofinvention comprises alternatively applying one layer of a chargedpolymeric material and one layer of a non-charged polymeric materialonto the surface of a polymeric article.

These and other aspects of the invention will become apparent from thefollowing description of the presently preferred embodiments. Thedetailed description is merely illustrative of the invention and doesnot limit the scope of the invention, which is defined by the appendedclaims and equivalents thereof. As would be obvious to one skilled inthe art, many variations and modifications of the invention may beeffected without departing from the spirit and scope of the novelconcepts of the disclosure.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Reference now will be made in detail to the embodiments of theinvention, one or more examples of which are set forth below. Eachexample is provided by way of explanation of the invention, and is not alimitation of the invention. In fact, it will be apparent to thoseskilled in the art that various modifications and variations can be madein the present invention without departing from the scope or spirit ofthe invention. For instance, features illustrated or described as partof one embodiment, can be used on another embodiment to yield a stillfurther embodiment. Thus, it is intended that the present inventioncovers such modifications and variations as come within the scope of theappended claims and their equivalents. Other objects, features andaspects of the present invention are disclosed in or are obvious fromthe following detailed description. It is to be understood by one ofordinary skill in the art that the present discussion is a descriptionof exemplary embodiments only, and is not intended as limiting thebroader aspects of the present invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Generally, the nomenclatureused herein and the laboratory procedures are well known and commonlyemployed in the art. Conventional methods are used for these procedures,such as those provided in the art and various general references. Wherea term is provided in the singular, the inventors also contemplate theplural of that term. As employed throughout the disclosure, thefollowing terms, unless otherwise indicated, shall be understood to havethe following meanings.

An “article” refers to a medical device or a mold for making a medicaldevice.

A “medical device”, as used herein, refers to a device having surfacesthat contact tissue, blood, or other bodily fluids of patients in thecourse of their operation or utility. Exemplary medical devices include:(1) extracorporeal devices for use in surgery such as blood oxygenators,blood pumps, blood sensors, tubing used to carry blood and the likewhich contact blood which is then returned to the patient; (2)prostheses implanted in a human or animal body such as vascular grafts,stents, pacemaker leads, heart valves, and the like that are implantedin blood vessels or in the heart; (3) devices for temporaryintravascular use such as catheters, guide wires, and the like which areplaced into blood vessels or the heart for purposes of monitoring orrepair; and (4) ophthalmic devices. In a preferred embodiment, medicaldevices are ophthalmic devices.

An “ophthalmic device”, as used herein, refers to a contact lens (hardor soft), an intraocular lens, a corneal onlay, other ophthalmic devices(e.g., stents, or the like) used on or about the eye or ocular vicinity,cases or containers for storing ophthalmic devices or ophthalmicsolutions.

“biocompatible”, as used herein, refers to a material or surface of amaterial, which may be in intimate contact with tissue, blood, or otherbodily fluids of a patient for an extended period of time withoutsignificantly damaging the ocular environment and without significantuser discomfort.

“Ophthalmically compatible”, as used herein, refers to a material orsurface of a material which may be in intimate contact with the ocularenvironment for an extended period of time without significantlydamaging the ocular environment and without significant user discomfort.Thus, an ophthalmically compatible contact lens will not producesignificant corneal swelling, will adequately move on the eye withblinking to promote adequate tear exchange, will not have substantialamounts of protein or lipid adsorption, and will not cause substantialwearer discomfort during the prescribed period of wear.

“Ocular environment”, as used herein, refers to ocular fluids (e.g.,tear fluid) and ocular tissue (e.g., the cornea) which may come intointimate contact with a contact lens used for vision correction, drugdelivery, wound healing, eye color modification, or other ophthalmicapplications.

A “monomer” means a low molecular weight compound that can bepolymerized. Low molecular weight typically means average molecularweights less than 700 Daltons.

A “macromer” refers to a medium and high molecular weight compound orpolymer that contains functional groups capable of furtherpolymerization. Medium and high molecular weight typically means averagemolecular weights greater than 700 Daltons.

“Polymer” means a material formed by polymerizing one or more monomers.

“Surface modification”, as used herein, means that an article has beentreated in a surface treatment process (or a surface modificationprocess), in which, by means of contact with a vapor or liquid, and/orby means of application of an energy source (1) a coating is applied tothe surface of an article, (2) chemical species are adsorbed onto thesurface of an article, (3) the chemical nature (e.g., electrostaticcharge) of chemical groups on the surface of an article are altered, or(4) the surface properties of an article are otherwise modified.Exemplary surface treatment processes include, but are not limited to, asurface treatment by energy (e.g., a plasma, a static electrical charge,irradiation, or other energy source), chemical treatments, the graftingof hydrophilic monomers or macromers onto the surface of an article, andlayer-by-layer deposition of polyelectrolytes. A preferred class ofsurface treatment processes are plasma processes, in which an ionizedgas is applied to the surface of an article. Plasma gases and processingconditions are described more fully in U.S. Pat. Nos. 4,312,575 and4,632,844, which are incorporated herein by reference. The plasma gas ispreferably a mixture of lower alkanes and nitrogen, oxygen or an inertgas.

“LbL coating”, as used herein, refers to a coating obtained by alayer-by-layer (“LbL”) alternative, physical deposition of twooppositely charged polymeric materials or of a charged polymericmaterial and a non-charged polymeric materials on an article. In an LbLcoating, each layer of a material is non-covalently bond to anotherlayer of a different material. Any suitable deposition techniques can beused in the LbL coating. Exemplary deposition techniques include,without limitation, dipping a substrate into a coating solution andspraying a substrate with a coating solution. A “charged polymericmaterial” or a polyionic material refers to a charged polymer that has aplurality of charged groups in a solution, or a mixture of chargedpolymers each of which has a plurality of charged groups in a solution.Exemplary charged polymers includes polyelectrolytes, p- and n-typedoped conducting polymers. Charged polymeric materials include bothpolycationic (having positive charges) and polyanionic (having negativecharges) polymeric materials.

The term “bilayer” is employed herein in a broad sense and is intendedto encompass, a coating structure formed by alternatively applying, inno particular order, one layer of a first charged polymeric material andone layer of a non-charged polymeric material or a second chargedpolymeric material. It should be understood that the layers of the firstcharged polymeric material and the non-charged polymeric material (orsecond charged polymeric material) may be intertwined with each other inthe bilayer.

An “innermost layer”, as used herein, refers to the first layer of anLbL coating, which is applied onto the surface of a medical device.

A “capping layer”, as used herein, refers to the last layer of an LbLcoating which is applied onto the surface of a medical device.

A “polyquat”, as used herein, refers to a polymeric quaternary ammoniumgroup-containing compound.

An “averaged value of coefficient of friction” refers to a value, whichis obtained by averaging measurements of at least 3 individual medicaldevices, as described in Example 10. Coefficient of friction(hereinafter CoF) may be one of important parameters that may affect theon-eye movement and thereby the wearer's comfort. High CoF may increasethe likelihood of damaging mechanically the ocular epithelia and/or maylead to ocular discomfort.

As used herein, “increased lubricity” in reference to a coated medicaldevice, e.g., a coated contact lens, means that the medical deuce has areduced averaged value of CoF relative to an uncoated medical device,wherein both coated and uncoated medical device are made of the samecore material.

An “average contact angle” refers to a contact angle (measured bySessile Drop method), which is obtained by averaging measurements of atleast 3 individual medical devices.

As used herein, “increased surface hydrophilicity” or “increasedhydrophilicity” in reference to a coated ophthalmic device means thatthe coated ophthalmic device has a reduced averaged contact anglerelative to an uncoated medical device, wherein both coated and uncoatedmedical device are made of the same core material.

The present invention, in one aspect, provides a method for producing amedical device having a core material and a biocompatible LbL coatingcomprising at least one layer of a charged polymeric material and onelayer of a non-charged polymeric material which can be non-covalentlybonded to the charged polymeric material. The method of the inventioncomprises contacting alternatively, in no particular order, with asolution of a charged polymeric material to form one layer of thecharged polymeric material and with a solution of a non-chargedpolymeric material, which can be bond non-covalently to the chargedpolymeric material, to form one layer of the non-charged polymericmaterial.

It has been discovered previously and disclosed in U.S. application Ser.No. 09/005,317 that complex and time-consuming pretreatment of a corematerial (medical device) is not required prior to binding of a chargedpolymeric material to the core material. By simply and alternativelycontacting a core material of a medical device, for example, a contactlens, with a solution of a first charged polymeric material and asolution of a second charged polymeric material having charges oppositeof the charges of the first charged polymeric material, amultiple-layered LbL coating can be formed on a medical device to modifythe surface properties of the core material of the medical device.

It has been discovered here that one layer of a charged polymericmaterial and one layer of a non-charged polymeric material, whichreplaces one of the two oppositely-charged polymeric materials, can bealternatively deposited onto a substrate to form a biocompatible LbLcoating, according to an unknown mechanism. Such coating can provide arelatively low surface charge density. It was quite unexpected to findthat the polymeric material which does not contain any charged groupscan also be physically (i.e., non-covalently) bonded to the chargedpolymeric material to create a multi-layered wear-resistant LbL coatingon a substrate. While the claimed invention is not limited to the theorydeveloped to support this unexpected result, a proposed theory ispresented herein in order to enable the reader to better understand theinvention. It is believed that there may exist some molecularinteractions between the charged groups of the charged polymericmaterial and the non-charged functional groups of the non-chargedpolymeric material so that complexation/precipitation of a layer of thenon-charged polymeric material may occurs on the layer of the chargedpolymeric material on a substrate.

The non-charged polymeric material according to the invention can be: ahomopolymer of a vinyl lactam; a copolymer of at least one vinyl lactamin the presence or in the absence of one or more hydrophilic vinyliccomonomers; or mixtures thereof.

The vinyl lactam has a structure of formula (I)

wherein

-   -   R is an alkylene di-radical having from 2 to 8 carbon atoms,    -   R₁ is hydrogen, alky, aryl, aralkyl or alkaryl, preferably        hydrogen or lower alkyl having up to 7 and, more preferably, up        to 4 carbon atoms, such as, for example, methyl, ethyl or        propyl; aryl having up to 10 carbon atoms, and also aralkyl or        alkaryl having up to 14 carbon atoms; and    -   R₂ is hydrogen or lower alkyl having up to 7 and, more        preferably, up to 4 carbon atoms, such as, for example, methyl,        ethyl or propyl.

Some N-vinyl lactams corresponding to the above structural formula (I)are N-vinyl-2-pyrrolidone, N-vinyl-2-piperidone, N-vinyl-2-caprolactam,N-vinyl-3-methyl-2-pyrrolidone, N-vinyl-3-methyl-2-piperidone,N-vinyl-3-methyl-2-caprolactam, N-vinyl-4-methyl-2-pyrrolidone,N-vinyl-4-methyl-2-caprolactam, N-vinyl-5-methyl-2-pyrrolidone,N-vinyl-5-methyl-2-piperidone, N-vinyl-5,5-dimethyl-2-pyrrolidone,N-vinyl-3,3,5-trimethyl-2-pyrrolidone,N-vinyl-5-methyl-5-ethyl-2-pyrrolidone,N-vinyl-3,4,5-trimethyl-3-ethyl-2-pyrrolidone,N-vinyl-6-methyl-2-piperidone, N-vinyl-6-ethyl-2-piperidone,N-vinyl-3,5-dimethyl-2-piperidone, N-vinyl-4,4-dimethyl-2-piperidone,N-vinyl-7-methyl-2-caprolactam, N-vinyl-7-ethyl-2-caprolactam,N-vinyl-3,5-dimethyl-2-caprolactam, N-vinyl-4,6-dimethyl-2-caprolactamand N-vinyl-3,5,7-trimethyl-2-caprolactam.

A preferred non-charged polymeric material is a polymer, copolymerderived from a vinyl lactam which is a heterocyclic monomer of formula(I) containing from 4 to 6 carbon atoms in the heterocyclic ring, or amixture thereof.

A more preferred non-charged polymeric material is a polymer, copolymerderived from a vinyl lactam which is a heterocyclic monomer of formula(I) containing 4 carbon atoms in the heterocyclic ring, or a mixturethereof.

An even more preferred non-charged polymeric material is a polymer,copolymer derived from a vinyl lactam which is a heterocyclic monomer offormula (I) containing 4 carbon atoms in the heterocyclic ring andwherein R₁ and R₂ are each independently of the other hydrogen or loweralkyl, or a mixture thereof.

A most preferred non-charged polymeric material is a polymer, copolymerderived from a vinyl lactam, which is N-vinyl-2-pyrrolidone, or amixture thereof.

Suitable hydrophilic vinylic comonomers include, without limitation,hydroxy-substituted lower alkylacrylates and -methacrylates, acrylamide,methacrylamide, lower alkyl-acrylamides and -methacrylamides,ethoxylated acrylates and methacrylates, hydroxy-substituted loweralkyl-acrylamides and -methacrylamides, hydroxy-substituted loweralkylvinyl-ethers, sodium ethylene sulphonate, sodium styrenesulphonate, 2-acrylamido-2-methyl-propane-sulphonic acid, N-vinylpyrrole, N-vinyl succinimide, N-vinyl pyrrolidone, 2- or 4-vinylpyridine, acrylic acid, methacrylic acid, amino- (whereby the term“amino” also includes quaternary ammonium), mono-lower-alkylamino- ordi-lower-alkylamino-lower-alkyl-acrylates and -methacrylates, allylalcohol and the like. Preference is given e.g. to hydroxy-substitutedC₂-C₄-alkyl(meth)acrylates, five- to seven-membered N-vinyl-lactams,N,N-di-C₁-C₄-alkyl-methacrylamides and vinylically unsaturatedcarboxylic acids with a total of 3 to 5 carbon atoms.

Where a homopolymer of a vinyl lactam; a copolymer of at least one vinyllactam in the presence or in the absence of one or more hydrophilicvinylic comonomers; or mixtures thereof is used as a non-chargedpolymeric material to build-up charge/non-charge bilayers of theinvention, a charged polymeric material is preferably a polyanionicpolymer or a mixture of polyanionic polymer. Examples of suitablepolyanionic polymers include, for example, a synthetic polymer, abiopolymer or modified biopolymer comprising carboxy, sulfo, sulfato,phosphono or phosphato groups or mixtures thereof, or a salt thereof,for example, a biomedical acceptable salt and especially anophthalmically acceptable salt thereof when the article to be coated isan ophthalmic device.

Examples of synthetic polyanionic polymers are: a linear polyacrylicacid (PAA), a branched polyacrylic acid, a polymethacrylic acid (PMA), apolyacrylic acid or polymethacrylic acid copolymer, a maleic or fumaricacid copolymer, a poly(styrenesulfonic acid) (PSS), a polyamido acid, acarboxy-terminated polymer of a diamine and a di- or polycarboxylic acid(e.g., carboxy-terminated Starburst™ PAMAM dendrimers from Aldrich), apoly(2-acrylamido-2-methylpropanesulfonic acid) (poly-(AMPS)), analkylene polyphosphate, an alkylene polyphosphonate, a carbohydratepolyphosphate or carbohydrate polyphosphonate (e.g., a teichoic acid).Examples of a branched polyacrylic acid include a Carbophil® orCarbopol® type from Goodrich Corp. Examples of a copolymer of acrylic ormethacrylic acid include a copolymerization product of an acrylic ormethacrylic acid with a vinylmonomer including, for example, acrylamide,N,N-dimethyl acrylamide or N-vinylpyrrolidone.

Examples of polyanionic biopolymers or modified biopolymers are:hyaluronic acid, glycosaminoglycanes such as heparin or chondroitinsulfate, fucoidan, poly-aspartic acid, poly-glutamic acid, carboxymethylcellulose, carboxymethyl dextranes, alginates, pectins, gellan,carboxyalkyl chitins, carboxymethyl chitosans, sulfated polysaccharides.

A preferred polyanionic polymer is a linear or branched polyacrylic acidor an acrylic acid copolymer. A more preferred anionic polymer is alinear or branched polyacrylic acid. A branched polyacrylic acid in thiscontext is to be understood as meaning a polyacrylic acid obtainable bypolymerizing acrylic acid in the presence of suitable (minor) amounts ofa di- or polyvinyl compound.

A suitable polycationic polymer as part of the bilayer is, for example,a synthetic polymer, biopolymer or modified biopolymer comprisingprimary, secondary or tertiary amino groups or a suitable salt thereof,preferably an ophthalmically acceptable salt thereof, for example ahydrohalogenide such as a hydrochloride thereof, in the backbone or assubstituents. Polycationic polymers comprising primary or secondaryamino groups or a salt thereof are preferred.

Examples of synthetic polycationic polymers are:

-   (i) a polyallylamine (PAH) homo- or copolymer, optionally comprising    modifier units;-   (ii) a polyethyleneimine (PEI);-   (iii) a polyvinylamine homo- or copolymer, optionally comprising    modifier units;-   (iv) a poly(vinylbenzyl-tri-C₁-C₄-alkylammonium salt), for example a    poly(vinylbenzyl-tri-methyl ammoniumchloride);-   (v) a polymer of an aliphatic or araliphatic dihalide and an    aliphatic N,N,N′,N′-tetra-C₁-C₄-alkyl-alkylenediamine, for example a    polymer of (a) propylene-1,3-dichloride or -dibromide or p-xylylene    dichloride or dibromide and (b)    N,N,N′,N′-tetramethyl-1,4-tetramethylene diamine;-   (vi) a poly(vinylpyridine) or poly(vinylpyridinium salt) homo- or    copolymer;-   (vii) a poly (N,N-diallyl-N,N-di-C₁-C₄-alkyl-ammoniumhalide)    comprising units of formula    -   wherein R₂ and R₂′ are each independently C₁-C₄-alkyl, in        particular methyl, and An⁻ is an anion, for example, a halide        anion such as the chloride anion;-   (viii) a homo- or copolymer of a quaternized    di-C₁-C₄-alkyl-aminoethyl acrylate or methacrylate, for example a    poly(2-hydroxy-3-methacryloylpropyltri-C₁-C₂-alkylammonium salt)    homopolymer such as a    poly(2-hydroxy-3-methacryloylpropyltri-methylammonium chloride), or    a quaternized poly(2-dimethylaminoethyl methacrylate or a    quaternized poly(vinylpyrrolidone-co-2-dimethylaminoethyl    methacrylate);-   (ix) POLYQUAD® as disclosed in EP-A-456,467; or-   (x) a polyaminoamide (PAMAM), for example a linear PAMAM or a PAMAM    dendrimer such as an amino-terminated Starbust™ PAMAM dendrimer    (Aldrich).

The above mentioned polymers comprise in each case the free amine, asuitable salt thereof, for example a biomedically acceptable salt or inparticular an ophthalmically acceptable salt thereof, as well as anyquaternized form, if not specified otherwise.

Suitable comonomers optionally incorporated in the polymers according to(i), (iii), (vi) or (viii) above are, for example, hydrophilic monomerssuch as acrylamide, methacrylamide, N,N-dimethyl acrylamide,N-vinylpyrrolidone and the like.

Suitable modifier units of the polyallylamine (i) are known, for examplefrom WO 00/31150 and comprise, for example, units of formula

wherein L is C₂-C₆-alkyl, which is substituted by two or more same, ordifferent substituents selected from the group consisting of hydroxy,C₂-C₅-alkanoyloxy and C₂-C₅-alkylamino-carbonyloxy.

Preferred substituents of the alkyl radical L are hydroxy, acetyloxy,propionyloxy, methyl-aminocarbonyloxy or ethylaminocarbonyloxy,especially hydroxy, acetyloxy or propionyloxy and in particular hydroxy.

L is preferably linear C₃-C₆-alkyl, more preferably linear C₄-C₅-alkyl,and most preferably n-pentyl, which is in each case substituted asdefined above. A particularly preferred radical L is1,2,3,4,5-pentahydroxy-n-pentyl.

Examples of polycationic biopolymers or modified biopolymers that may beemployed in the bilayer of the present invention include: basicpeptides, proteins or glucoproteins, for example, a poly-ε-lysine,albumin or collagen, aminoalkylated polysaccharides such as a chitosanor aminodextranes.

Particular polycationic polymers for forming the bilayer of the presentinvention include a polyallylamine homopolymer; a polyallylaminecomprising modifier units of the above formula (II); a polyvinylaminehomo- or -copolymer or a polyethyleneimine homopolymer, in particular apolyallylamine or polyethyleneimine homopolymer, or apoly(vinylamine-co-acrylamid) copolymer.

The foregoing lists are intended to be exemplary, but clearly are notexhaustive. A person skilled in the art, given the disclosure andteaching herein, would be able to select a number of other usefulcharged polymeric materials.

In order to alter various characteristics of the coating, such asthickness, the molecular weight of the charged polymeric materials andnon-charged polymeric materials can be varied. In particular, as themolecular weight is increased, the coating thickness generallyincreases. However, if the increase in molecular weight increase is toosubstantial, the difficulty in handling may also increase. As such,coating materials including charged polymeric and non-charged polymericmaterials used in a process of the present invention will typically havea molecular weight M_(n) of about 2,000 to about 150,000. In someembodiments, the molecular weight is about 5,000 to about 100,000, andin other embodiments, from about 75,000 to about 100,000.

In accordance with the present invention, the core material of a medicaldevice may be any of a wide variety of polymeric materials. Exemplarycore materials include, but are not limited to, hydrogels,silicone-containing hydrogels, polymers and copolymers of styrene andsubstituted styrenes, ethylene, propylene, acrylates and methacrylates,N-vinyl lactams, acrylamides and methacrylamides, acrylonitrile, acrylicand methacrylic acids.

A preferred group of core materials to be coated are those beingconventionally used for the manufacture of biomedical devices, e.g.contact lenses, in particular contact lenses for extended wear, whichare not hydrophilic per se. Such materials are known to the skilledartisan and may comprise for example polysiloxanes, perfluoroalkylpolyethers, fluorinated poly(meth)acrylates or equivalent fluorinatedpolymers derived e.g. from other polymerizable carboxylic acids,polyalkyl (meth)acrylates or equivalent alkylester polymers derived fromother polymerizable carboxylic acids, or fluorinated polyolefines, suchas fluorinated ethylene or propylene, for example tetrafluoroethylene,preferably in combination with specific dioxols, such asperfluoro-2,2-dimethyl-1,3-dioxol. Examples of suitable bulk materialsare e.g. Lotrafilcon A, Neofocon, Pasifocon, Telefocon, Silafocon,Fluorsilfocon, Paflufocon, Silafocon, Elastofilcon, Fluorofocon orTeflon AF materials, such as Teflon AF 1600 or Teflon AF 2400 which arecopolymers of about 63 to 73 mol % of perfluoro-2,2-dimethyl-1,3-dioxoland about 37 to 27 mol % of tetrafluoroethylene, or of about 80 to 90mol % of perfluoro-2,2-dimethyl-1,3-dioxol and about 20 to 10 mol % oftetrafluoroethylene.

Another group of preferred core materials to be coated isamphiphilic-segmented copolymers comprising at least one hydrophobicsegment and at least one hydrophilic segment, which are linked through abond or a bridge member. Examples are silicone hydrogels, for examplethose disclosed in PCT applications WO 96/31792 to Nicolson et al. andWO 97/49740 to Hirt et al.

A particular preferred group of core materials to be coated comprisesorganic polymers selected from polyacrylates, polymethacrylates,polyacrylamides, poly(N,N-dimethylacrylamides), polymethacrylamides,polyvinyl acetates, polysiloxanes, perfluoroalkyl polyethers,fluorinated polyacrylates or -methacrylates and amphiphilic segmentedcopolymers comprising at least one hydrophobic segment, for example apolysiloxane or perfluoroalkyl polyether segment or a mixedpolysiloxane/perfluoroalkyl polyether segment, and at least onehydrophilic segment, for example a polyoxazoline,poly(2-hydroxyethylmethacrylate), polyacrylamide,poly(N,N-dimethylacrylamide), polyvinylpyrrolidone polyacrylic orpolymethacrylic acid segment or a copolymeric mixture of two or more ofthe underlying monomers.

The core material to be coated may also be any blood-contacting materialconventionally used for the manufacture of renal dialysis membranes,blood storage bags, pacemaker leads or vascular grafts. For example, thematerial to be modified on its surface may be a polyurethane,polydimethylsiloxane, polytetrafluoroethylene, polyvinylchloride,Dacron™ or Silastic™ type polymer, or a composite made therefrom.

The contacting of the medical device with a solution of, either acharged polymeric material, a non-charged polymeric material or arinsing solution, may occur by a variety of methods. For example, themedical device may be dipped into a solution. Alternatively, the medicaldevice is sprayed with a solution in a spray or mist form. One coatingprocess embodiment involves solely dip-coating and optionallydip-rinsing steps. Another coating process embodiment involves solelyspray-coating and optionally spray-rinsing steps. Of course, a number ofalternatives involve various combinations of spray- and dip-coating andoptionally spray- and dip-rinsing steps may be designed by a personhaving ordinary skill in the art.

For example, a solely dip-coating process involves the steps ofimmersing a medical device in a solution of a charged polymericmaterial; optionally rinsing the medical device by immersing the medicaldevice in a rinsing solution; immersing said medical device in asolution of a non-charged polymeric material which can be non-covalentlybond to the charged polymeric material on the medical device; andoptionally rinsing said medical device in a rinsing solution, thereby toform a bilayer of the charged polymeric material and the non-chargedpolymeric material. This bilayer formation process may be repeated aplurality of times in order to produce a thicker LbL coating.

The immersion time for each of the coating and optional rinsing stepsmay vary depending on a number of factors. Preferably, immersion of thecore material into a coating solution occurs over a period of about 1 to30 minutes, more preferably about 1 to 20 minutes, and most preferablyabout 1 to 5 minutes. Rinsing may be accomplished with a plurality ofrinsing steps, but a single rinsing step, if desired, can be quiteefficient.

Another embodiment of the coating process involves a series of spraycoating techniques. The process generally includes the steps of sprayinga core material of a medical device with a solution of a chargedpolymeric material; optionally rinsing the medical device by sprayingthe medical device with a rinsing solution and then optionally dryingthe medical device; spraying the medical device with a solution of anon-charged polymeric material which can be non-covalently bond to thecharged polymeric material on the medical device; optionally rinsing themedical device by spraying the medical device with a rinsing solution,thereby to form a bilayer of the charged polymeric material and thenon-charged polymeric material. This bilayer formation procedure may berepeated a plurality of times in order to produce a thicker LbL coating.

The spray coating application may be accomplished via a process selectedfrom the group consisting of an air-assisted atomization and dispensingprocess, an ultrasonic-assisted atomization and dispensing process, apiezoelectric assisted atomization and dispensing process, anelectromechanical jet printing process, a piezo-electric jet printingprocess, a piezo-electric with hydrostatic pressure jet printingprocess, and a thermal jet printing process; and a computer systemcapable of controlling the positioning of the dispensing head of thespraying device on the ophthalmic lens and dispensing the coatingliquid. Those spraying coating processes are described in U.S.Application No. 60/312,199, herein incorporated by reference in itsentirety. By using such spraying coating processes, an asymmetricalcoating can be applied to a medical device. For example, the backsurface of a contact lens can be coated with a hydrophilic and/orlubricous coating material and the front surface of the contact lens canbe coated with an antimicrobial material. It is also possible to producea coating on a contact lens, the coating having a functional pattern soas to provide simultaneously multiple benefits to a wearer.

A preferred number of bilayers in a biocompatible LbL coating of theinvention are about 5 to about 20 bilayers. While more than 20 bilayersare possible, it has been found that delamination may occur in some LbLcoatings having an excessive number of bilayers.

A biocompatible LbL coating of the invention can comprise at least onelayer of a first charged polymeric material and at least one layer of asecond charged polymeric material, wherein the first and second chargedpolymeric material have the same sign of charges.

A biocompatible LbL coating of the invention can comprise at least onelayer of a first non-charged materials and at least one layer of asecond non-charged polymeric material, wherein each of the first andsecond non-charged polymeric materials can be bond non-covalently toadjacent layers of a charged polymeric material.

A biocompatible LbL coating of the invention can comprise one or morebilayers of a first charged polymeric material and a second chargedpolymeric material having charges opposite of the charges of the firstcharged polymeric material.

In accordance with the present invention, coating solutions can beprepared in a variety of ways. In particular, a coating solution of thepresent invention can be formed by dissolving a charged polymericmaterial or a non-charged polymeric material in water or any othersolvent capable of dissolving the materials. When a solvent is used, anysolvent that can allow the components within the solution to remainstable in water is suitable. For example, an alcohol-based solvent canbe used. Suitable alcohol can include, but are not limited to, isopropylalcohol, hexanol, ethanol, etc. It should be understood that othersolvents commonly used in the art can also be suitably used in thepresent invention.

Whether dissolved in water or in a solvent, the concentration of acoating material (i.e., a charged polymeric material or a non-chargedpolymeric material) in a solution of the present invention can generallyvary depending on the particular materials being utilized, the desiredcoating thickness, and a number of other factors.

It may be typical to formulate a relatively dilute aqueous solution ofcharged polymeric material. For example, a charged polymeric materialconcentration can be between about 0.0001% to about 0.25% by weight,between about 0.005% to about 0.10% by weight, or between about 0.01% toabout 0.05% by weight.

However, where a coating solution containing a first charged polymericmaterial is used to form an innermost layer of a biocompatible LbLcoating of the invention on the surface of a medical device, it isdesirable that the concentration of the first charged polymeric materialin the solution is sufficiently high enough to increase thehydrophilicity of the LbL coating. It is discovered that theconcentration of a charged polymeric material in a solution for formingthe innermost layer of an LbL coating has a direct significant impact onthe hydrophilicity of the LbL coating on a contact lens. When theconcentration of the charged polymeric material increases, thehydrophilicity of the LbL coating increases. Preferably, theconcentration of the charged polymeric material in a solution forforming the innermost layer of an LbL coating is at least three folderhigher than the concentration of a coating material in a coatingsolution for forming subsequent layers of the LbL coating. Morepreferably, the concentration of the charged polymeric material in asolution for forming the innermost layer of an LbL coating is at leastten folder higher than the concentration of a coating material in acoating solution for forming subsequent layers of the LbL coating.

In general, the charged polymeric solutions mentioned above can beprepared by any method well known in the art for preparing solutions.For example, in one embodiment, a polyanionic solution can be preparedby dissolving a suitable amount of the polyanionic material, such aspolyacrylic acid having a molecular weight of about 90,000, in watersuch that a solution having a certain concentration is formed. In oneembodiment, the resulting solution is a 0.001M PAA solution. Oncedissolved, the pH of the polyanionic solution can also be adjusted byadding a basic or acidic material. In the embodiment above, for example,a suitable amount of 1N hydrochloric acid (HCl) can be added to adjustthe pH to 2.5.

Solutions of a polycationic material or non-charged polymeric materialcan also be formed in a manner as described above. For example, in oneembodiment, poly(allylamine hydrochloride) having a molecular weight ofabout 50,000 to about 65,000 can be dissolved in water to form a 0.001MPAH solution. Thereafter, the pH can also be adjusted to 2.5 by adding asuitable amount of hydrochloric acid.

In some embodiments of the invention, the coating process for forming abiocompatible LbL coating on a medical device comprises: applying,directly onto the core material of a medical device, one or more bilayerof a first charged polymeric material and a second charged polymericmaterial having charges opposite of the charges of the first chargedpolymeric material; and then applying one or more bilayers of the first(or second) charged polymeric material and a non-charged polymericmaterial which can be non-covalently bond to the first (or second)charged polymeric material.

Where a biocompatible LbL coating comprises at least one bilayer of afirst charged polymeric material and a second charged polymeric materialhaving charges opposite of the charges of the first charged polymericmaterial, it may be desirable to apply a solution containing both thefirst and second charged polymeric materials within a single solution.For example, a polyanionic solution can be formed as described above,and then mixed with a polycationic solution that is also formed asdescribed above. The solutions can then be mixed slowly to form acoating solution. The amount of each solution applied to the mix dependson the molar charge ratio desired. For example, if a 10:1(polyanion:polycation) solution is desired, 1 part (by volume) of thePAH solution can be mixed into 10 parts of the PAA solution. Aftermixing, the solution can also be filtered if desired.

An LbL coating of the present invention may find particular use inextended-wear contact lenses. The LbL coating of the invention may havea minimal adverse effects on the desirable bulk properties of the lens,such as oxygen permeability, ion permeability, and optical properties.

The present invention, in another aspect, provides a medical devicehaving a core material and an LbL coating formed thereon and a surfacehydrophilicity characterized by having an average contact angle of about80 degrees or less, wherein the LbL coating comprises at least onebilayer composed of one layer of a charged polymeric material and onelayer of a non-charged polymeric material which can be non-covalentlybonded to the charged polymeric material. Preferably, the coated medicaldevice has an increased lubricity characterized by an average CoF ofabout 3.5 or less.

A medical device of the invention can be made by applying abiocompatible LbL coating to a preformed medical device according to anabove-described method of the invention.

A medical device of the invention can also be made by first applying abiocompatible LbL coating to a mold for making a medical device and thentransfer-grafting the biocompatible LbL coating to the medical devicemade from the mold, in substantial accordance with the teachings of U.S.patent application (Ser. No. 09/774,942), herein incorporated byreference in its entirety.

Methods of forming mold sections for cast-molding a contact lens aregenerally well known to those of ordinary skill in the art. The processof the present invention is not limited to any particular method offorming a mold. In fact, any method of forming a mold can be used in thepresent invention. However, for illustrative purposes, the followingdiscussion has been provided as one embodiment of forming a transferablebiocompatible LbL coating on a mold and then making a contact lens witha biocompatible LbL coating thereon from the coated mold in accordancewith the present invention.

In general, a mold comprises at least two mold sections (or portions) ormold halves, i.e. first and second mold halves. The first mold halfdefines a first optical surface and the second mold half defines asecond optical surface. The first and second mold halves are configuredto receive each other such that a contact lens-forming cavity is formedbetween the first optical surface and the second optical surface. Thefirst and second mold halves can be formed through various techniques,such as injection molding. These half sections can later be joinedtogether such that a contact lens-forming cavity is formed therebetween.Thereafter, a contact lens can be formed within the contact lens-formingcavity using various processing techniques, such as ultraviolet curing.

Examples of suitable processes for forming the mold halves are disclosedin U.S. Pat. No. 4,444,711 to Schad; U.S. Pat. No. 4,460,534 to Boehm etal, U.S. Pat. No. 5,843,346 to Morrill; and U.S. Pat. No. 5,894,002 toBoneberger et al., which are also incorporated herein by reference.

Virtually all materials known in the art for making molds can be used tomake molds br making contact lenses. For example, polymeric materials,such as polyethylene, polypropylene, and PMMA can be used. Othermaterials that allow UV light transmission could be used, such as quartzglass.

Once a mold is formed, a transferable biocompatible LbL coating, whichcomprises at least one bilayer of a charged polymeric material and anon-charged polymeric material, can be applied onto the optical surface(inner surface) of one or both mold portions by using theabove-described LbL deposition techniques. The inner surface of a moldportion is the cavity-forming surface of the mold and in direct contactwith lens-forming material. A transferable biocompatible LbL coating canbe applied onto the mold portion defining the posterior (concave)surface of a contact lens or on the mold section defining the anteriorsurface of a contact lens or on both mold portions.

Once a transferable biocompatible LbL coating is applied onto theoptical surface of one or both mold portions, a lens material can thenbe dispensed into the contact lens forming cavity defined by theassembled mold halves. In general, a lens material can be made from anypolymerizable composition. In particular, when forming a contact lens,the lens material may be an oxygen-permeable material, such as fluorine-or siloxane-containing polymer. For example, some examples of suitablesubstrate materials include, but are not limited to, the polymericmaterials disclosed in U.S. Pat. No. 5,760,100 to Nicolson et al, whichis incorporated herein by reference. The lens material can then becured, i.e. polymerized, within the contact lens-forming cavity to formthe contact lens, whereby at least a portion of the transferablebiocompatible LbL coating detaches from the optical surface andreattaches to the formed contact lens.

Thermal curing or photo curing methods can be used to curing apolymerizable composition in a mold to form an ophthalmic lens. Suchcuring methods are well-known to a person skilled in the art.

In addition to charged and non-charged polymeric materials, a coatingsolution for forming the bilayer or part of it, can also containadditives. As used herein, an additive can generally include anychemical or material. For example, active agents, such as antimicrobialsand/or antibacterials can be added to a solution forming the bilayer,particularly when used in biomedical applications. Some antimicrobialcharged polymeric materials include polyquaternary ammonium compounds,such as those described in U.S. Pat. No. 3,931,319 to Green et al. (e.g.POLYQUAD®).

Moreover, other examples of materials that can be added to a coatingsolution are materials useful for ophthalmic lenses, such as materialshaving radiation absorbing properties. Such materials can include, forexample, visibility-tinting agents, iris color modifying dyes, andultraviolet (UV) light tinting dyes.

Still another example of a material that can be added to a coatingsolution is a material that inhibits or induces cell growth. Cell growthinhibitors can be useful in devices that are exposed to human tissue foran extended time with an ultimate intention to remove (e.g. catheters orIntra Ocular Lenses (IOL's), where cell overgrowth is undesirable),while cell growth-inducing charged polymeric materials can be useful inpermanent implant devices (e.g. artificial cornea).

When additives are applied to a coating solution, such additives,preferably, have a charge. By having a positive or negative charge, theadditive can be substituted for the charged polymeric material insolution at the same molar ratio. For example, polyquaternary ammoniumcompounds typically have a positive charge. As such, these compounds canbe substituted into a solution of the present invention for thepolycationic component such that the additive is applied to the corematerial of an article in a manner similar to how a polycationic wouldbe applied.

It should be understood, however, that non-charged additives can also beapplied to the core material of an article by entrapment.

Moreover, the core material to be coated may also be an inorganic ormetallic base material without suitable reactive groups, e.g. ceramic,quartz, or metals, such as silicon or gold, or other polymeric ornon-polymeric substrates. e.g., for implantable biomedical applications,ceramics are very useful. In addition, e.g. for biosensor purposes,hydrophilically coated base materials are expected to reduce nonspecificbinding effects if the structure of the coating is well controlled.Biosensors may require a specific carbohydrate coating on gold, quartz,or other non-polymeric substrates.

The form of the material to be coated may vary within wide limits.Examples are particles, granules, capsules, fibers, tubes, films ormembranes, preferably moldings of all kinds such as ophthalmic moldings,for example intraocular lenses, artificial cornea or in particularcontact lenses.

The previous disclosure will enable one having ordinary skill in the artto practice the invention. In order to better enable the reader tounderstand specific embodiments and the advantages thereof, reference tothe following examples is suggested.

EXAMPLE 1 Measurements of CoF of Coated Contact Lenses

COF may be one of parameters that measure the easiness of the on-eyemovement of a contact lens. High CoF may increase the likelihood ofdamaging mechanically the ocular epithelia. CoF of a contact lens can bemeasured by a sled-on-block type of friction tester as follow. Under acertain load (e.g., about 2.0 grams), a contact lens is slid back andforth, at a prescribed speed, against a biologically relevant substrateand both the normal force (N) and the tangential force (FT) aremeasured. The CoF of the contact lens is calculated based on theequation of μ=F_(T)/N.

A preferred friction tester comprises: a stationary lens holderassembly, a biologically relevant substrate, a horizontally movableplatform, and a plurality of force measuring means.

The stationary lens holder assembly preferably comprises an “A-shaped”holder bracket and a lens holder having a lens-supporting surface. Thelens-supporting surface of the lens holder has a convex curvaturecapable of accommodating the back (concave) surface of a contact lens.The lens holder is preferably held by a means in the center of the“A-shaped” holder bracket. The head end of the “A-shaped” stationarysample holder bracket is connected to a first force measuring means(e.g., a load cell from Transducer Techniques) by, for example, aKevlar® fiber. The two foot-ends of the “A-shaped” holder bracket areconnected to nylon string attached with two ½″ steel extension springs.The first force measuring means and the steel extension springs aremounted to the frame of the tester.

The horizontally movable platform can be, for example, a table platform(x-table) which moves uniaxially at various speeds and accelerations.The x-table preferably has a dimension of 163 mm long and 19.1 mm wideand can provide a test area having about 140 mm long and about 14.7 mmwide. An example of the x-table is a Model 41 Linear Positioner, whichis powered by a ZETA Drive Compumotor (Parker Hannifin Corporation),which operates unidirectional at maximum velocities of 1800 mm/min andaccelerations of 9000 mm/s².

The biologically relevant substrate can be any material and preferablyis a powder-free surgical glove with Biogel® Coating” from Regent®.Preferably, the finger of the glove is cut into a single rectangularstrip, and stretched and attached to the x-table by a physical means,for example, jumbo paper clips. Before testing, the substrate attachedonto the x-table is lubricated with two drops of a desired lubricant,for example, ultra pure water or Softwear® saline (CIBA vision). Any airbetween the substrate and the x-table should be removed. The desiredlubricant should be applied evenly on the substrate. The substrateshould be even and consistent throughout.

Preferably, there are three force-measuring means, a first, a second anda third force-measuring means. Any suitable known force measuring meanscan be used. An example is a 100-gram load cells from TransducerTechniques. The first force-measuring means is attached to the sampleholder to measure tangential forces (friction forces, FT) in twoopposite directions. The second and third force measuring means resideunder the x-table to measure normal force (N) in the downward direction.The other load cell Values outputted by the normal load cells areconverted to grams by a Versatile Amplifier/Conditioner (TransducerTechniques).

Measurements of CoF are performed on the preferred friction tester asfollows. A contact lens is placed on a lens holder with the back surfaceof the contact lens against the lens-supporting surface of the lenshold. The lens holder with the contact lens is assembled with the“A-shaped” holder bracket and then placed in contact with a desiredlubricated substrate. This substrate is mounted to a horizontallymovable table platform that is capable of moving uniaxially at variousspeeds and accelerations. About 3 grams of weight is loaded onto thelens holder. This load may represent the force pressed on a contact lensby a blink of eyelids. The three force-measuring means (3 Load cellsfrom Transducer Techniques) measure simultaneously the normal (N) andfrictional (FT) forces that are produced from the interaction betweenthe contact lens and the substrate lubricated with a desired lubricant.Multiple data points are taken during a measurement oflubricity/lubricating drag/coefficient of friction of a contact lens. Ateach data point, CoF μ, is calculated as follows:μ=F _(T) /Nin which F_(T) represent actual data reading at each point obtained bythe first force measuring means after correcting for the preloadingprovided by the springs (tangential load cell) during sliding of thesubstrate against the contact lens and preferably has a unit of gram; Nis the sum of N₁ and N2; N1 represents actual data reading at each pointobtained by the second force-measuring means after correcting for anypreloading by the test assembly (normal load cell#1) during sliding ofsubstrate against the contact lens and preferably has a unit of gram;and N₂ represents actual data reading at each point obtained by thethird force-measuring means after correcting for any preloading by thetest assembly (normal load cell#2) during sliding of substrate againstthe contact lens and has preferably a unit of gram. The average(μ_(Ave)) of all μ's at every data point will be used to represent thevalue of CoF of a contact lens.

More preferably, the friction tester further comprises a computer systemthat controls the tester, collects readings of the normal and tangentialforces simultaneously as the biologically-relevant substrate interactswith contact lens, calculates CoF, and records and charts the forces(F_(T) and N) and CoF (μ) at each data point during testing.

EXAMPLE 2 Measurements of Contact Angles of Coated Contact Lenses

Average contact angles (Sessile Drop) of contact lenses are measuredusing a VCA 2500 XE contact angle measurement device from AST, Inc.,located in Boston, Mass. This equipment is capable of measuringadvancing or receding contact angles or sessile (static) contact angles.The measurements are preferably performed on fully hydrated materials.

The contact angle is a general measure of the surface hydrophilicity ofa contact lens. In particular, a low contact angle corresponds to morehydrophilic surface. The averaged contact angle of a contact lens, whichis made of lotrafilcon A and without any coating (LbL or plasma), isabout 112 degree.

EXAMPLE 3

Polyacrylic acid (PAA) solution: A solution of polyacrylic acid having amolecular weight of about 90,000, from PolyScience, is prepared bydissolving a suitable amount of the material in water to form a 0.001MPAA solution. The PAA concentration is calculated based on the repeatingunit in PAA. Once dissolved, the pH of the polyanionic PAA solution isadjusted by adding 1N hydrochloric acid until the pH is about 2.5.

Poly(allylamine hydrochloride) (PAH) solution: A solution ofpoly(allylamine hydrochloride) (PAH) having a molecular weight of about70,000, from Aldrich, is prepared by dissolving a suitable amount of thematerial in water to form a 0.001M PAH solution. The concentration iscalculated based on the molecular weight of repeating unit in PAH.Thereafter, the pH of the polycationic PAH solution is measured andrecorded. The pH is around 4.5

Polyvinylpyrrolidone (PVP) solution: A solution of polyvinylpyrrolidone(PVP, from Aldrich) having a molecular weight of 55,000 is prepared bydissolving a suitable amount of the material in water to form a 0.01MPVP solution. The concentration is calculated based on the repeatingunit in PVP. Once dissolved, the pH of the PVP solution is adjusted byadding 1N hydrochloric acid until the pH is about 2.5.

Coating: A LbL coating having a capping layer of PVP is formed on asilicon wafer as follows. Initially, a silicon wafer is dipped in thePAH solution (0.001M, pH2.5) for 30 minutes, optionally rinsed with arinsing solution (water or acidified water at pH 2.5) for 1 minute,dipped in the PAA solution (0.001M, pH 2.5) for 5 minutes, optionallyrinsed with the rinsing solution for 1 minute, dipped in the PAHsolution for 5 minutes, and optionally rinsed with the rinsing solutionfor 1 minute. The silicon wafer having a coating composed three layers(PAH/PAA/PAH) is dipped in the PAA solution for 5 minutes, optionallyrinsed with the rinsing solution for 1 minute, dipped in the PVPsolution, optionally rinsed with the rinsing solution. By repeating theabove dipping and optionally rinsing steps for a desired number of timesto form a desired number of bilayers of PAA/PVP with a capping layer ofPVP.

Table 1 reports the thickness of a coating on silicon wafer. Thethickness of the coating on a Si wafer increases from about 9 nm (5layers) to about 30 nm (11 layers), indicating that PAA and PVP canself-assemble into multi-layers. It is also found that themulti-bilayers of PAA/PVP can be assembled with or without water rinsesteps. TABLE 1 Number of Thickness Thickness Thickness Coating Layers(nm)¹ (nm)² (nm)³ PAH/PAA/PAH/(PAA/ 5  8.5 ± 0.5  8.0 ± 1.3  9.7 ± 0.6PVP) PAH/PAA/PAH/(PAA/ 7 14.3 ± 0.6 16.8 ± 3.1 15.7 ± 1.4 PVP)₂PAH/PAA/PAH/(PAA/ 9 21.8 ± 1.3 30.5 ± 5.4 20.6 ± 4.6 PVP)₃PAH/PAA/PAH/(PAA/ 11 29.1 ± 2.3 31.1 ± 4.4 27.4 ± 2.9 PVP)₄¹There is a rinsing step by dipping in water (neutral) between twodipping steps.²There is a rinsing step by dipping in water (pH 2.5) between twodipping steps.³There is no rinsing step between two dipping steps

When a silicon wafer having an LbL coating consisting of five layers(PAH/PAA/PAH/PAA/PVP) is exposed to an acidified water (pH 2.5) for 30minutes, there is no significant change in the thickness of the coatingon a silicon wafer (i.e., the thickness changes from 8.5±0.5 to8.6±1.5).

When a silicon wafer having an LbL coating consisting of seven layers(PAH/PAA/PAH/PAA/PVP/PAA/PVP) is subjected to an autoclave process inbalanced salt solution (BSS) (pH 7.2), a patch-wise pattern can beobserved on the resultant Si wafer and the thickness of the coating on asilicon wafer increases from 14.3±0.6 to 20.4±10.

When a silicon wafer having an LbL coating consisting of nine layers(PAH/PAA/PAH/PAA/PVP/PAA/PVP/PAA/PVP) is subjected to an autoclaveprocess in water, there is no significant change in the thickness of thecoating on a silicon wafer (i.e., the thickness changes from 21.8±1.3 to19.1±2.9).

When a silicon wafer having an LbL coating consisting of eleven layers(PAH/PAA/PAH/PAA/PVP/PAA/PVP/PAA/PVP/PAA/PVP) is exposed to a phosphatebuffered saline (PBS) (ca. pH 7.2), the thickness of the coating on asilicon wafer decreases from 29.1±2.3 to 3.3±0.3. However, when thissilicon wafer is further subjected to an autoclave process in PBSbuffer, the thickness of the coating on a silicon wafer increases from3.3±0.3 to 51.9±10.6.

EXAMPLE 4

PAA and PVP solutions: PAA and PVP solutions are prepared as describedin Example 3.

Coating: A LbL coating having a capping layer of PVP is formed on a softcontact lens made of a fluorosiloxane hydrogel material, lotrafilcon A(CIBA Vision). The contact lens is initially dipped in the PAA solution(0.001 M, pH 2.5) for 30 minutes, optionally rinsed with a rinsingsolution (acidified water at pH 2.5) for 1 minute, then dipped in thePVP solution (0.01 M, ca. pH 2.5) for 5 minutes, and optionally rinsedwith the rinsing solution for 1 minute. The above-described dipping andrinsing steps are repeated for a desired number of times to form abiocompatible LbL coating on the lens. Each of the coated lenses isplaced and sealed in one glass vial filled with PBS buffer andautoclaved. After autoclave, vials containing a coated lens are notopened until lens characterization.

The coated contact lenses are not stained by Sudan black (SB),indicating that the contact lens is fully covered by the coating. Asseen from table 2, PAA/PVP multi-layers were also successfully used tocoat contact lenses. After only 6 dips, the coated lenses have contactangles of about 75 to 85 degrees and COF of about 3.4 (as compared toabout a COF of 4 for un-coated lenses). TABLE 2 SB Coating Contactangle^(a) COF staining Uncoated contact lens 110 ˜4.0 stain (Control)PAA/PVP/PAA/PVP/ 75 ± 10^(b) 76 ± 10^(c) 3.46 ± 0.28 clear PAA/PVP^(d)PAA/PVP/PAA/PVP/ 80 ± 3^(b)  85 ± 10^(c) 3.44 ± 0.14 clear PAA/PVP^(e)^(a)A value obtained by averaging the measurements of three contactlenses.^(b)Determined before autoclave.^(c)Determined after autoclave.^(d)There is a rinsing step (dipping in water at pH 2.5 for 1 minute)between two dipping steps.^(e)There is no rinsing step between two dipping steps.

EXAMPLE 5

PAA and PVP solutions: PAA and PVP solution are prepared as described inExample 3.

PAAm-o-PAA solution: A solution of PAAm-co-PAA copolymer (80% PAAm ad20% PAA, from Advanced Research Unit, Ciba Vision Switzerland) isprepared by dissolving a suitable amount of the material in water toform a 0.0001M solution. The PAAm-co-PAA copolymer concentration iscalculated based on the molecular weight of repeat unit. Once dissolved,the pH of the PAAm-co-PAA solution is adjusted to pH 2.5 by adding 1Nhydrochloric acid.

Coating A: A coating having multiple bilayers of PVP/PAAm-co-PAA isformed on a silicon wafer or a soft contact lens made of afluorosiloxane hydrogel material, lotrafilcon A (CIBA Vision). Thecontact lens (or silicon wafer) is dipped in the PAA solution (0.001M,pH 2.5) for 30 minutes to form a first layer on the lens. The lens (orsilicon wafer) with a first layer of PAA is then dipped in the PVPsolution (0.0001M, pH 2.5) for 5 minutes and then dipped in thePAAm-co-PAA solution for 5 minutes. Finally, the steps of dipping in thePVP solution for 5 minutes followed by dipping in the PAAm-co-PAAsolution for 5 minutes are repeated for a desired number of times tobuild up a desired number of bilayers of PVP/PAAm-co-PAA on the lens (orsilicon wafer). There is no rinsing step involved in the above coatingprocess. Each of the coated lenses is placed and sealed in one glassvial filled with PBS buffer and autoclaved. After autoclave, vialscontaining a coated lens are not opened until lens characterization.

Silicon wafers and contact lenses with LbL coatings, which comprises twoor more bilayers of PVP/PAAm-co-PAA are characterized and results arereported in Table 3. TABLE 3 Thickness Contact Coating (nm)^(a)angle^(b) PAA/PVP/PAAm-co-PAA/PVP/PAAm-co-PAA 6.0 ± 1.2 58 ± 10PAA/PVP/PAAm-co-PAA/PVP/PAAm-co- 8.7 ± 2.1 29 ± 2 PAA/PVP/PAAm-co-PAA/PVP/PAAm-co-PAA^(a)Determined on Si wafers.^(b)determined on lenses.

The experimental results confirm that an LbL coating comprisingmulti-bilayer of PVP/PAAm-co-PAA can be successfully applied onto asilicon wafer or a contact lens. The coated lenses have a contact anglesof about 58 degrees when having one layer of PAA and 2 bilayers ofPVP/PAAm-co-PAA and have a contact angles of about 30 degrees whenhaving one layer of PAA and 4 bilayers of PVP/PAAm-co-PAA. The uncoatedcontact lenses have a contact angles of about 110 degrees.

EXAMPLE 6

PAA solution: A PAA solution is prepared as described in Example 3.

PVP solution: A PVP solution is prepared according to a proceduresimilar to that described in Example 3. The concentration of PVP is0.001 M (pH 2.5).

PVP-co-PAA solution: A solution of PVP-co-PAA copolymer (75% PVP ad 25%PAA, from Aldrich, is prepared by dissolving a suitable amount of thematerial in water to form a 0.001M solution. The PVP-co-PAA copolymerconcentration is calculated based on the molecular weight of repeatunit. Once dissolved, the pH of the PVP-co-PAA solution is adjusted topH 2.5.

PQ6-10 solution: A solution of polyquat (PQ6-10) of the followingformula

in which R₁, R₂, R₃, and R₄ are methyl radicals, and A and B arehexamethylene and decamethylene groups respectively, is prepared bydissolving a suitable amount of PQ6-10 in water to have a concentrationof 300 ppm. Once dissolved, the pH of the PQ6-10 solution is adjusted topH 5.6.

Coating A: A coating having the innermost layer of PAA, 4 bilayers ofPVP/PVP-co-PAA and one capping bilayer of PVP/PAA (i.e.,PAA/PVP/PVP-co-PAA/PVP/PVP-co-PAA/PVP/PVP-co-PAA/PVP/PVP-co-PAA/PVP/PAA)is formed on a silicon wafer or a soft contact lens made of afluorosiloxane hydrogel material, lotrafilcon A (CIBA Vision). Thecontact lens (or silicon wafer) is dipped in the PAA solution (0.001M,pH 2.5) for 30 minutes to form the innermost layer of the coating on thelens. The lens (or silicon wafer) with the innermost layer of PAA isthen dipped in the PVP solution (0.0001M, pH 2.5) for 5 minutes and thendipped in the PVP-co-PAA solution for 5 minutes. The steps of dipping inthe PVP solution for 5 minutes followed by dipping in the PVP-co-PAAsolution for 5 minutes are repeated for 4 times to build up 4 bilayersof PVP/PVP-co-PAA on the lens (or silicon wafer). The lens (or siliconwafer) with the innermost layer of PAA and 4 bilayers of PVP/PVP-co-PAAis dipped in the PVP solution for 5 minute and then dipped in the PAAsolution. There is no rinsing step involved in the above coatingprocess. Each of the coated lenses is placed and sealed in one glassvial filled with PBS buffer and autoclaved. After autoclave, vialscontaining a coated lens are not opened until lens characterization.

Coating B: A coating having the innermost layer of PAA, 4 bilayers ofPVP/PVP-co-PAA, one bilayer of PVP/PAA and a capping layer of PQ6-10(i.e.,PAA/PVP/PVP-co-PAA/PVP/PVP-co-PAA/PVP/PVP-co-PA/PVP/PVP-co-PAA/PVP/PAA/PQ6-10)is formed on a silicon wafer or a soft contact lens made of afluorosiloxane hydrogel material, lotrafilcon A (CIBA Vision). Thecontact lens (or silicon wafer) is dipped in the PAA solution (0.001M,pH 2.5) for 30 minutes to form the innermost layer of the coating on thelens. The lens (or silicon wafer) with the innermost layer of PAA isthen dipped in the PVP solution (0.0001M, pH 2.5) for 5 minutes and thendipped in the PVP-co-PAA solution for 5 minutes. The steps of dipping inthe PVP solution for 5 minutes followed by dipping in the PVP-co-PAAsolution for 5 minutes are repeated for 4 times to build up 4 bilayersof PVP/PVP-co-PAA on the lens (or silicon wafer). The lens (or siliconwafer) with the innermost layer of PAA and 4 bilayers of PVP/PVP-co-PAAis dipped in the PVP solution for 5 minute, then dipped in the PAAsolution, and finally dipped in the PQ6-10 solution. There is no rinsingstep involved in the above coating process. Each of the coated lenses isplaced and sealed in one glass vial filled with PBS buffer andautoclaved. After autoclave, vials containing a coated lens are notopened until lens characterization.

Silicon wafers and contact lenses with LbL coatings are characterizedand results are reported in Table 4. TABLE 4 Thickness Contact Coating(nm)^(a) angle^(b) A (PAA/PVP/PVP-co-PAA/PVP/PVP-co- 7 36 ± 3PAA/PVP/PVP-co-PAA/PVP/PVP-co- PAA/PVP/PAA) B(PAA/PVP/PVP-co-PAA/PVP/PVP-co- 17 25 ± 4 PAA/PVP/PVP-co-PAA/PVP/PVP-co-PAA/PVP/PAA/PQ6-10)^(a)Determined on Si wafers.^(b)Determined on lenses.

The experimental results confirm that an LbL coating (coating A orcoating B) can be successfully applied onto a silicon wafer or a contactlens. The coated lenses have a substantially increased hydrophilicitycharacterized by a contact angles of about 36 degrees for coating A anda contact angles of about 25 degrees for coating B. The uncoated contactlenses have a contact angles of about 110 degrees.

EXAMPLE 7

PAA solutions: Three PAA solutions (pH 2.5) respectively containing0.0001 M, 0.001 M and 0.01 M PAA are prepared as described in Example 3.

PVP solution: A PVP solution is prepared according to a proceduresimilar to that described in Example 3.

Coating: A LbL coating having a multi-bilayer of PAA/PVP is formed on asoft contact lens made of a fluorosiloxane hydrogel material,lotrafilcon A (CIBA Vision). The contact lens is initially dipped in afirst PAA solution (0.0001M, 0.001 M or 0.01 M, pH2.5) for 30 minutes toform the innermost layer of the coating. The lens with the innermostlayer of PAA is dipped in the PVP solution (0.0001M, about pH 2.5) for 5minutes and then dipped in a PAA solution (0.0001 M, pH 2.5). The stepsof dipping in the PVP solution (0.0001M, about pH 2.5) and dipping inthe PAA solution (0.0001M, about pH 2.5) are repeated for 4 times. Acapping layer of PVP is applied to the coated lens by dipping in the PAAsolution (0.0001M, about pH 2.5). Each of the coated lenses is placedand sealed in one glass vial filled with PBS buffer and autoclaved.After autoclave, vials containing a coated lens are not opened untillens characterization.

It is found that the PAA concentration used in the formation of theinnermost layer has significant effect on the hydrophilicity of coatedcontact lenses. The contact angle obtained by averaging measurements of10 contact lenses (before autoclave) decreases from 59±8 degrees, to43±7 degrees and to 38±9 degrees, when the concentration of PAAincreases from 0.0001 M, to 0.001M, to 0.01 M. Similarly, the contactangle obtained by averaging measurements of 10 contact lenses (afterautoclave) decreases from 65±7 degrees, to 54±5 degrees and to 52±7degrees, when the concentration of PAA increases from 0.0001M, to0.001M, to 0.010 M. The uncoated contact lenses have a contact angle ofabout 110 degrees.

EXAMPLE 8

PAA, PAH and PVP solutions: PAA, PAH, PVP solutions are prepared asdescribed in Example 3.

An LbL coating procedure is tried to build up multibilayers of PAH/PVPon a silicon wafer. The silicon wafer is dipped in the PAH solution(0.0001 M, pH2.5) for 30 minutes, optionally rinsed with a rinsingsolution (acidified water pH 2.5) for 1 minute, dipped in the PVPsolution (0.0001M, approx. pH 2.5) for 5 minutes, and the optionallyrinsed with the rinsing solution for 1 minute. By repeating the 5-minutedip coating steps first in the PAH solution and then in the PVP solutionand optionally 1 minute-rinsing step between two dip-coating step for anumber of times (3, 5, 7, 9 times). After the LbL coating process iscompleted, the thickness of coating on the silicon wafer is determinedand results are reported in Table 5. Table 5 shows that the thickness ofa coating on the silicon wafer does not increase as the number ofiterative dip-coatings increases, indicating that multi-bilayers ofPAH/PVP may not be efficiently built-up on a silicon wafer under thecoating conditions in the study. TABLE 5 Coating Thickness SuccessiveCoating Solutions (nm)^(a) PAH, PVP, PAH, PVP, PAH, PVP, PAH, PVP 2.7 ±0.4 PAH/PVP, PAH, PVP, PAH, PVP, PAH, PVP, PAH, PVP, 2.4 ± 0.2 PAH, PVPPAH/PVP, PAH, PVP, PAH, PVP, PAH, PVP, PAH, PVP, 3.2 ± 0.6 PAH, PVP,PAH, PVP, PAH, PVP PAH/PVP, PAH, PVP, PAH, PVP, PAH, PVP, PAH, PVP, 3.2± 0.5 PAH, PVP, PAH, PVP, PAH, PVP, PAH, PVP, PAH, PVP^(a)Averaged coating thickness on a silicon wafer is determined byaveraging the measurements of 4 silicon wafers.

Although various embodiments of the invention have been described usingspecific terms, devices, and methods, such description is forillustrative purposes only. The words used are words of descriptionrather than of limitation. It is to be understood that changes andvariations may be made by those skilled in the art without departingfrom the spirit or scope of the present invention, which is set forth inthe following claims. In addition, it should be understood that aspectsof the various embodiments may be interchanged either in whole or inpart. Therefore, the spirit and scope of the appended claims should notbe limited to the description of the preferred versions containedtherein.

1-14. (canceled)
 15. A method for producing a medical device having abiocompatible LbL coating, comprising the steps of: (a) contacting saidmedical device with a solution of a charged polymeric material to form alayer of the charged polymeric material, (b) optionally rinsing saidmedical device by contacting said medical device with a rinsingsolution; (c) contacting said medical device with a solution of anon-charged polymeric material to form a layer of the non-chargedmaterial on top of the layer of the charged polymeric material, whereinthe non-charged polymeric material is capable of being non-covalentlybond to the charged polymeric material in said biocompatible LbLcoating; and (d) optionally rinsing said medical device by contactingsaid medical device with the rinsing solution.
 16. A method of claim 15,wherein said charged polymeric material is a first polyanionic polymeror a mixture of two or more polyanionic polymers, and wherein saidnon-charged material is a homopolymer of a vinyl lactam of formula (I),a opolymer of at least one vinyl lactam of formula (I) in the presenceor in the absence of one or more hydrophilic vinylic comonomers, ormixture thereof

wherein R is an alkylene di-radical having from 2 to 8 carbon atoms, R₁is hydrogen, C₁-C₁₀ alkyl, aryl having up to 10 carbon atoms, aralkyl oralkaryl having up to 14 carbon atoms, and R₂ is hydrogen or C₁-C₁₀alkyl.
 17. A method of claim 15, wherein at least one of said contactingoccurs by immersion said medical device in a solution.
 18. A method ofclaim 15, wherein at least one of said contacting occurs by spraying asolution onto the medical device.
 19. A method of claim 15, wherein saidmethod comprises repeating steps (a) through (d) between 3 to 20 times.20. A method of claim 15, comprising a step of contacting the medicaldevice with a first-dipping solution of a charged polymeric material toform an innermost layer of said coating on the surface of the medicaldevice, wherein the concentration of the charged material in thefirst-dipping solution is sufficiently high enough to increase thehydrophilicity of the LbL coating.
 21. A method for producing a contactlens having a biocompatible LbL coating, comprising the steps of: (a)forming a mold for making the contact lens, wherein the mold comprises afirst mold portion having a first optical surface and a second moldportion having a second optical surface, wherein said first mold portionand said second mold portion are configured to receive each other suchthat a contact lens-forming cavity is formed between said first opticalsurface and said second optical surface; (b) applying a transferablebiocompatible LbL coating, using a layer-by-layer deposition technique,onto at least one of said optical surface, wherein the transferablebiocompatible LbL coating comprises at least one charge/non-chargebilayer, wherein said charge/non-charge bilayer is composed of, in noparticular order, one layer of a charged polymeric material and onelayer of a non-charged polymeric material which is capable of beingnon-covalently bond to the charged polymeric material; (c) positioningsaid first mold portion and said second mold portion such that said moldportions receive each other and said optical surfaces define saidcontact lens forming cavity; (d) dispensing a polymerizable compositioninto said contact lens-forming cavity; and (e) curing said polymerizablecomposition within said contact lens-forming cavity such that thecontact lens is formed, whereby said transferable biocompatible LbLcoating detaches from said at least one optical surface of said moldportion and reattaches to said formed contact lens such that saidcontact lens becomes coated with the biocompatible LbL coating.
 22. Amethod of claim 21, wherein said transferable biocompatible LbL coatingis applied onto at least one of said optical surfaces in a processcomprising steps of: (a) contacting said at least one of said opticalsurfaces with a solution of a charged polymeric material to form a layerof the charged polymeric material; (b) optionally rinsing said at leastone of said optical surfaces by contacting said at least one of saidoptical surfaces with a rinsing solution; (c) contacting said at leastone of said optical surfaces with a solution of a non-charged polymericmaterial to form a layer of the non-charged polymeric material on top ofthe layer of the charged polymeric material, wherein the non-chargedpolymeric material is capable of being non-covalently bond to thecharged polymeric material in said biocompatible LbL coating; and (d)optionally rinsing said at least one of said optical surfaces bycontacting said at least one of said optical surfaces with the rinsingsolution.
 23. A method of claim 22, wherein at least one of saidcontacting occurs by immersion said at least one of said opticalsurfaces in a solution.
 24. A method of claim 22, wherein at least oneof said contacting occurs by spraying a solution onto said at least oneof said optical surfaces.
 25. A method of claim 22, wherein said methodcomprises repeating steps (a) through (d) between 3 to 20 times.
 26. Amethod of claim 22, wherein said charged polymeric material is a firstpolyanionic polymer or a mixture of two or more polyanionic polymers,and wherein said non-charged material is a homopolymer of a vinyl lactamof formula (I), a coplymer of at least one vinyl lactam of formula (I)in the presence or in the absence of one or more hydrophilic vinyliccomonomers, or mixture thereof

wherein R is an alkylene di-radical having from 2 to 8 carbon atoms, R₁is hydrogen, C₁-C₁₀ alkyl, aryl having up to 10 carbon atoms, aralkyl oralkaryl having up to 14 carbon atoms, and R₂ is hydrogen or C₁-C₁₀alkyl.
 27. A method of claim 26, wherein at least one of said contactingoccurs by immersion said medical device in a solution.
 28. A method ofclaim 26, wherein at least one of said contacting occurs by spraying asolution onto the medical device.
 29. A method of claim 26, wherein saidmethod comprises repeating steps (a) through (d) between 3 to 20 times.30. A method of claim 26, wherein the capping layer of said transferablebiocompatible LbL coating is a layer of the charged polymeric material.